Exploring the pharmacological mechanism of Glycyrrhiza uralensis against KOA through integrating network pharmacology and experimental assessment.

Knee osteoarthritis (KOA), a major health and economic problem facing older adults worldwide, is a degenerative joint disease. Glycyrrhiza uralensis Fisch. (GC) plays an integral role in many classic Chinese medicine prescriptions for treating knee osteoarthritis. Still, the role of GC in treating KOA is unclear. To explore the pharmacological mechanism of GC against KOA, UPLC-Q-TOF/MS was conducted to detect the main compounds in GC. The therapeutic effect of GC on DMM-induced osteoarthritic mice was assessed by histomorphology, µCT, behavioural tests, and immunohistochemical staining. Network pharmacology and molecular docking were used to predict the potential targets of GC against KOA. The predicted results were verified by immunohistochemical staining Animal experiments showed that GC had a protective effect on DMM-induced KOA, mainly in the improvement of movement disorders, subchondral bone sclerosis and cartilage damage. A variety of flavonoids and triterpenoids were detected in GC via UPLC-Q-TOF/MS, such as Naringenin. Seven core targets (JUN, MAPK3, MAPK1, AKT1, TP53, RELA and STAT3) and three main pathways (IL-17, NF-κB and TNF signalling pathways) were discovered through network pharmacology analysis that closely related to inflammatory response. Interestingly, molecular docking results showed that the active ingredient Naringenin had a good binding effect on anti-inflammatory-related proteins. In the verification experiment, after the intervention of GC, the expression levels of pp65 and F4/80 inflammatory indicators in the knee joint of KOA model mice were significantly downregulated. GC could improve the inflammatory environment in DMM-induced osteoarthritic mice thus alleviating the physiological structure and dysfunction of the knee joint. GC might play an important role in the treatment of knee osteoarthritis.

Bearing surface defect detection based on improved convolutional neural network.

This paper addresses the issue of artificial visual inspection being overly reliant on subjective experience and the difficulty for the human eye to accurately identify dense and non-significant defects. To solve this problem, we have implemented an automatic object detection algorithm based on an improved version of YOLOv5.First, we use the K-means++ clustering algorithm to automatically calculate the Anchor of the model to reduce the effect of the close location of the initial clustering centers on the clustering of the sample data.Second, we add the Coordinate Attention (CA) attention mechanism to the model to allow the model to better capture and understand important features in the images. Then, we add a new detection layer with a downsampling multiplier of 4 to the Neck network to improve the precision of the model. Finally, we use the lightweight network MobileNetV3 instead of YOLOv5's backbone network to reduce the model detection time overhead.Our model achieves 85.87% mAP, which is 6.44% better than the YOLOv5 network, and the detection time for a single image is only 54ms, which is 50% faster than the YOLOv5 network. After testing, we have proven that our proposed algorithm can quickly and accurately detect the condition of bearing appearance defects, improving detection efficiency and reducing costs.

Chromosomal microdeletion leading to pituitary gigantism through hormone-gene overexpression.

Pituitary gigantism is a rare endocrinopathy characterized by tall stature due to growth hormone (GH) hypersecretion. This condition is generally linked to a genetic predisposition to tumors that produce GH or GH-releasing hormone (GHRH). Here, we report a Japanese woman who exhibited prominent body growth from infancy to reach an adult height of 197.4 cm (+7.4 standard deviation). Her blood GH levels were markedly elevated. She carried no pathogenic variants in known growth-controlling genes but had a hitherto unreported 752 kb heterozygous deletion at 20q11.23. The microdeletion was located 8.9 kb upstream of GHRH and encompassed exons 2-9 of a ubiquitously expressed gene TTI1 together with 12 other genes, pseudogenes and non-coding RNAs. Transcript analyses of the patient's leukocytes showed that the microdeletion produced chimeric mRNAs consisting of exon 1 of TTI1 and all coding exons of GHRH. In silico analysis detected promoter-associated genomic features around TTI1 exon 1. Genome-edited mice carrying the same microdeletion recapitulated accelerated body growth from a few weeks after birth. The mutant mice developed pituitary hyperplasia and exhibited ectopic Ghrh expression in all tissues examined. Thus, the extreme phenotype of pituitary gigantism in the patient likely reflects GHRH overexpression driven by an acquired promoter. The results of this study indicate that germline submicroscopic deletions have the potential to cause conspicuous developmental abnormalities due to gene overexpression. Furthermore, this study provides evidence that constitutive expression of a hormone-encoding gene can result in congenital disease.

Optimized Hierarchical Structure and Chemical Gradients Promote the Biomechanical Functions of the Spike of Mantis Shrimps.

The tail spike of the mantis shrimp is the appendage for counteracting the enemy from behind. Here, we investigate the correlations between the chemical compositions, the microstructures, and the mechanical properties of the spike. We find that the spike is a hollow beam with a varying cross section along the length. The cross section comprises four different layers with distinct features of microstructures and chemical compositions. The local mechanical properties of these layers correlate well with the microstructures and chemical compositions, a combination of which effectively restricts the crack propagation while maximizing the release of strain energy during deformation. Finite element analysis and mechanics modeling demonstrate that the optimized structure of the spike confines the mechanical damage in the region near the tip and prevents catastrophic breakage at the base. Furthermore, we use a 3D printing technique to fabricate multiple hollow cylindrical samples consisting of biomimetic microstructures of the spike and confirm that the combination of the Bouligand structure with radially oriented parallel sheets greatly improves the toughness and strength during compression tests. The multiscale design strategy of the spike revealed here is expected to be of great interest for the development of novel bioinspired materials.

Investigation of the relationship between adhesion force and mechanical behavior of vertically aligned carbon nanotube arrays.

The mechanical behavior of vertically aligned carbon nanotube (VACNT) arrays can largely impact their adhesion performance. In this paper, we fabricated various VACNT arrays to investigate the relationship between adhesion force and their mechanical behavior. High-volume fraction (3.4%) CNT arrays did not exhibit the applicable adhesion effect due to their intrinsic elastic property. Adhesion measurements on several low-density (less than 0.5%) VACNT arrays demonstrated that the adhesion performance is strongly related to the plastic deformation of the carbon nanotubes at the contact surface. Due to the nature of the growth of CNT arrays, the top region of the as-grown CNT arrays is denser and stiffer than the bottom region of the arrays. Therefore, compared with as-grown CNT arrays, the flipped CNT arrays reached higher adhesion efficiency (the ratio of adhesion force to preload) with lower preload due to the higher compliance at the top surface of the arrays. With cyclic loading under micro mechanical tests, stiffening of the surface and declining of adhesion force were also observed. These results illustrated that the mechanical compliance at the region near the contact interface is the dominant factor for the adhesion performance of VACNT arrays.

Focusing on appraisals: how and why anger and fear influence driving risk perception.

INTRODUCTION: The present research explores how and why anger and fear influence driving risk perception. METHODS: Based on appraisal tendency framework, researchers hypothesized that anger and fear would influence driving risk perception in opposite directions due to their differences in appraisals. RESULTS: Study 1 showed that anger reduced risk perception, whereas fear increased it. In Studies 2, 3, and 4, the researchers adopted the paradigm of reappraisal to investigate the causes of the opposite effects found in Study 1. Consistent with our hypothesis, appraisals accounted for these effects: After reappraisals along the dimensions of certainty (Study 2), control (Study 3), and responsibility (Study 4), the different effects between anger and fear on driving risk perception diminished or disappeared. In addition, fearful or angry experience mediated the effects of reappraisals on driving risk perception. IMPACT ON INDUSTRY: The findings highlight the necessity to differentiate anger and fear in road safety management. Additionally, the current research also provides feasible methods (e.g., certainty, control, or responsibility reappraisal) to intervene in driving risk perception, which is important for driving safety.

The role of emotions in risk communication.

We present two experiments investigating the role of emotions concerning technological and natural hazards. In the first experiment, technological hazards aroused stronger emotions, and were considered to be riskier than natural hazards. No differences were found between the texts versus audio presentations. However, the presence of pictures aroused stronger emotions and increased the perceived risk. Emotions play a mediating role between hazard types and perceived risk, as well as between pictures and perceived risk. The second experiment adopted real-world materials from webpages and TV. Emotions again play a mediating role between pictorial information and risk perception. Moreover, specific emotions were found to be associated with different types of action tendencies. For example, loss-based emotions (e.g., fear, regret) tend to lead to prevention strategies, whereas ethical emotions (e.g., anger) lead to aggressive behavior. We also find that loss-based emotions in the technical hazard scenario trigger more coping strategies (from prevention to retaliation) than in the natural hazard scenario.